1H-Pyrrolo(2,3-b)pyridine → Tert-butyl 4-(1H-pyrrolo[2,3-B]pyridin-3-YL)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 988565Notes

Reaction equation

HRID 988565 reaction equation
[NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1.[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][C:20](=O)[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].[OH-].[K+]>CO>[C:10]([O:14][C:15]([N:17]1[CH2:18][CH:19]=[C:20]([C:3]2[C:4]3[C:5](=[N:6][CH:7]=[CH:8][CH:9]=3)[NH:1][CH:2]=2)[CH2:21][CH2:22]1)=[O:16])([CH3:13])([CH3:11])[CH3:12]

Participants

5

Reactant 3

HCID 92221H-Pyrrolo(2,3-b)pyridineHCID 14797Potassium HydroxideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 45790246Tert-butyl 4-(1H-pyrrolo[2,3-B]pyridin-3-YL)-5,6-dihydropyridine-1(2H)-carboxylateYield 91%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1H-Pyrrolo[2,3-b]pyridine (3 g, 25 mmol), 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (4.2 g, 21 mmol) and potassium hydroxide (3.56 g, 63 mmol) were added in MeOH (60 mL) and heated to reflux for 16 h. The reaction mixture was then cooled to room temperature and poured into ice water (300 mL). The mixture was extracted with 10% MeOH/CH2Cl2 (5×150 mL). The organic extracts was dried over Na2SO4 and concentrated to form a solid. The solid was washed with MeOH (150 mL), filtered and dried to give a light yellow solid 5.7 g (91%). TLC (silica, 50% EtOAc/hexanes): Rf=0.3. MS (electrospray): exact mass calculated for C17H21N3O2, 299.16; m/z found, 300.2 [M++H]. 1H NMR (CDCl3, 400 MHz) 10.97 (br s, 1H), 8.33 (dd, J=3.33 Hz, 1.37 Hz, 1H), 8.20 (dd, J=6.65 Hz, 1.37 Hz, 1H), 7.34 (br s, 1H), 7.25 (s, 1H), 7.13 (dd, J=4.89 Hz, 3.13 Hz, 1H), 4.14 (br s, 2H), 3.68 (t, J=5.28 Hz, 2H), 2.56 (br s, 2H), 1.49 (s, 9H).

Workup

  1. temperatureheated
  2. temperatureto reflux for 16 h
  3. extractionThe mixture was extracted with 10% MeOH/CH2Cl2 (5×150 mL)
  4. dry with materialThe organic extracts was dried over Na2SO4
  5. concentrationconcentrated
  6. customto form a solid
  7. washThe solid was washed with MeOH (150 mL)
  8. filtrationfiltered
  9. customdried

Sources & evidence

ORD record
ord-b53441950fff4498af54766e68e2bb4c
Source dataset
uspto-grants-2003_10
Patent number
US06635633B2

Reaction notes

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